Topical anesthetic for dental procedures

ABSTRACT

A topical anesthetic for dental procedures is provided containing about 3 wt % to 10 wt % tetracaine in a vehicle suitable for administration to the oral mucosa. The vehicle for transporting the tetracaine includes a water soluble mucoadhesive or a combination of mucoadhesives such as a high molecular weight poly(ethylene oxide) homopolymer and a cellulose polymer. The vehicle may additionally include a penetration enhancer such as propylene glycol. The tetracaine is ground into a powder and is suspended in a plasticized hydrocarbon gel which completes the vehicle.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a topical anesthetic containing tetracaine as the sole anesthetic agent in a delivery vehicle suitable for administration to the oral mucosa prior to a dental procedure.

2. Brief Description of the Prior Art

The literature is replete with references to tetracaine hydrochloride as an anesthetic agent frequently in combination with one or more other anesthetic agents, e.g., lidocaine, benzocaine, cocaine, etc.

The most common topical dental anesthetic is 20% benzocaine in a gel. Benzocaine also comes in a spray form, mainly for pediatric use. The products are usually flavored to mask the bitter, unpleasant taste of benzocaine. The flavoring in the anesthetic tends to stimulate the flow of saliva so that the anesthetic tends to be washed away from the application site. It may also be necessary to aspirate the saliva and clear the field before starting a procedure.

There is a need for a more effective topical anesthetic for dental procedures. Twenty percent benzocaine in gel or spray form is not a highly effective dental anesthetic. There have been studies showing that it is little better than a placebo for muting the pain of an injection; the main benefit being that the patient thinks that something has been done for his or her comfort. The anesthetic effect of benzocaine is also of short duration.

BRIEF SUMMARY OF THE INVENTION

In view of the above, it is an object of the present invention to provide a more effective topical anesthetic for dental procedures. It is another object to provide a vehicle for delivering tetracaine with efficacy as a topical dental anesthetic. It is also an object to provide an essentially tasteless topical dental anesthetic that does not stimulate the production of saliva. Other objects and features of the invention will be in part apparent and in part pointed out hereinafter.

In accordance with the present invention, a topical anesthetic for dental procedures is provided containing about 3 wt % to 10 wt % tetracaine in a vehicle suitable for administration to the oral mucosa. The topical anesthetic binds to the oral mucosa and a sufficient amount of the tetracaine is transported into the mucosa in about three to five minutes to provide profound anesthesia at the application site. The anesthetic effect has a duration of about one to one and one-half hours. The topical anesthetic improves subsequent injection comfort and may allow for other procedures to be performed without an injection.

The vehicle for transporting the tetracaine includes a water soluble mucoadhesive or a combination of mucoadhesives such as a high molecular weight poly(ethylene oxide) homopolymer and a cellulose polymer. The vehicle may additionally include a penetration enhancer such as propylene glycol. The tetracaine is ground into a powder and is suspended in a plasticized hydrocarbon gel which completes the vehicle.

The invention summarized above comprises the compositions hereinafter described, the scope of the invention being indicated by the subjoined claims.

DETAILED DESCRIPTION OF THE INVENTION

A topical anesthetic composition is provided for administration to the oral mucosa prior to a dental procedure. In an embodiment, the composition is in paste form but the composition may be formulated as a gel if desired. As compared to conventional topical anesthetics, the subject anesthetic composition has improved efficacy, potency, convenience and duration when applied to the oral mucosa of a patient prior to a dental procedure. In an embodiment of the present invention, the topical anesthetic for dental procedures contains tetracaine and a mucoadhesive in a plasticized hydrocarbon gel. In another embodiment, the composition additionally contains a penetration enhancer to facilitate penetration of the tetracaine into the mucosa.

The tetracaine is provided in base form, i.e., not as the hydrochloride salt. Tetracaine is a white, or light yellow, waxy solid melting in the range of 41° to 46° C. It is very slightly soluble in water; soluble in alcohol, ether, benzene and chloroform. The amount of tetracaine in the formulation will vary depending on the desired therapeutic effect and duration of anesthesia needed. In one embodiment of the of the present invention, the concentration of the tetracaine is from about 3 wt % to 10 wt % of the total composition to deliver an effective dosage. In another embodiment, the concentration of the tetracaine is from about 4 wt % to 8 wt % of the total composition. In yet another other embodiment, the concentration of the tetracaine is about 6 wt %.

One or more mucoadhesives is included in the composition. As used herein the term mucoadhesive means a natural or synthetic substance, e.g., gels, pastes, macromolecules, polymers, and oligomers, or mixtures thereof, that can adhere to a subject's mucous membrane for a period of time sufficient to locally deliver a therapeutically-effective amount of tetracaine. The composition itself need not be mucoadhesive, as long as it can form a mucoadhesive upon on the contact with the mucosa.

Examples of mucoadhesives for use in the present invention include, but are not limited to, pectin, alginic acid, chitosan, hyaluronic acid, polysorbates, such as polysorbate-20, -21, -40, -60, -61, -65, -80, -81, -85; poly(ethyleneglycol), such as PEG-7, -14, -16, -18, -55, -90, -100, -135, -180, -4, -240, -6, -8, -9, -10, -12, -20, or -32; oligosaccharides and polysaccharides, such as gellan, carrageenan, xanthan gum, gum arabic, and dextran; cellulose esters and cellulose ethers; modified cellulose polymers, such as carboxymethylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl ethylcellulose; polyether polymers and oligomers, such as polyoxyethylene; condensation products of poly(ethyleneoxide) with various reactive hydrogen containing compounds having long hydrophobic chains, condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols; polyether compounds, such as poly(methyl vinyl ether), polyoxypropylene of less than 10 repeating units; polyether compounds, such as block copolymers of ethylene oxide and propylene oxide; ORABASE® (i.e., a mixture of gelatine, pectin and sodium carboxymethyl cellulose in a plasticized hydrocarbon gel, commercially available from Hoyt laboratories, Needhm, Mass.).

It is preferred that the mucoadhesive be water soluble and that a combination of mucsoadhesives be used. Homopolyers of ethylene oxide are particularly preferred in combination with a second mucoadhesive such as sodium carboxymethylcellulose. Commercially available homopolymers of ethylene oxide are sold under the trademark POLYOX by Dow Chemical Company, Midland, Mich. POLYOX poly(ethylene oxide) polymers have a number of important properties for mucoadhesion—namely, water solubility, hydrophilicity, high molecular weight, hydrogen bonding functionality, and good biocompatibility. The polymers have a long linear chain structure which allows them to form a strong interpenetrating network with mucus. Data indicates that poly(ethylene oxide) polymers with a molecular weight of 4,000,000 and higher have the highest level of adhesion. The amount of mucoadhesive in the formulation depends upon the mucoadhesives selected and the consistency desired in the composition. One embodiment of the topical anesthetic composition makes use of POLYOX WSR 301 which has a molecular weight of 4,000,000 in combination with sodium carboxymethylcellulose medium viscosity. In this embodiment, the combined mucoadhesive makes up 10 wt % of the formula with POLYOX WSR 301 comprising about 3 wt % to about 8 wt % of the combination. In the absence of a mucoadhesive like POLYOX WSR 301, the topical adhesive tends to migrate from the site of application, spreading the numbing action of the tetracaine to unintended areas.

The topical anesthetic composition of the present invention may include a penetration enhancer to increase the absorption of the tetracaine into the mucosa. A suitable penetration enhance should have no irritancy or toxicity to the mucosa, as well as high penetration enhancing effects. The penetration enhancers should be physicochemically stable and not have pharmacologic effects and preferably should not have disagreeable smell, color or taste. One embodiment uses propylene glycol as the penetration enhancer. Other glycols, monohydric alcohols, and fatty acid glycerides may also serve as penetration enhancers. When propylene glycol is the penetration enhancer, it may be present in the topical anesthetic composition in an amount from about 5 wt % to 15 wt %. When the poly (ethylene oxide) homopolymer is present in an amount of about 5 wt % and the sodium carboxymethylcellulose is present in an amount of about 4 wt %, it may be preferred that the propylene glycol be present in an amount of about 10 wt % as larger amounts of propylene glycol may render the paste too fluid to stay in place at the site of application.

A plasticized hydrocarbon gel completes the carrier vehicle for tetracaine in the topical anesthetic of the present invention. The plasticized hydrocarbon gel may be mixture of polyethylene in mineral oil. The plasticized hydrocarbon gel keeps the paste from dissolving away quickly, giving tetracaine time to penetrate. In one embodiment, the plasticized hydrocarbon gel makes up about 70 wt % of the formula.

The topical anesthetic compositions may include preservatives. Preferably, if present, the preservative comprises no more than about 1 wt %, but may vary depending on the other components.

The topical anesthetic compositions of the present invention may be prepared using ordinary production methods. In one embodiment, the composition is prepared as described in Example 1.

To relieve pain from dental procedures involving the gums or palate, the compositions of the invention are topically applied directly to the treatment area. The treatment area may be dried with a cotton swab and the composition then applied with a cotton applicator such as a Q-tip. It is not necessary to tightly control the dosage applied. If applied with a Q-tip, most operators will generally apply about 10 mg of paste. Less or more paste, for example from about 8 to 16 mg may be applied without toxic effect or raising an allergic reaction in most people. The larger amount may be needed to anesthetize the entire palate.

Unlike most common dental anesthetics, the anesthetic composition of the present invention has essentially no taste so there is no need to add a flavoring. The anesthetic composition tends to stay on the application site for effective absorption of the tetracaine, which effect occurs in about three to five minutes after application. There may be a synergistic effect between the delivery vehicle and the tetracaine as the anesthetic effect (i.e., efficacy and potency of the tetracaine) is greater than was expected. Since the anesthetic composition has no flavor, it does not stimulate the flow of saliva which results in a drier field. Generally the treatment area does not need to be dried or rinsed prior to or after injection (if injection is needed).

The anesthetic composition improves injection comfort and allows for other procedures to be performed without the use of what typically requires an injection of Novocain. Procedures such as scaling and root planing, gross debridement, Tofflimiere application, and tissue retained extractions may be performed without use of infiltration of any kind. The anesthetic composition has also been used without infiltration during crown or bridge procedures on teeth which have gone through root canal therapy, whether in the maxillary or mandibular region.

The following examples 2-6 illustrate the invention while Example 7 is for purposes of comparison therewith.

EXAMPLE 1

A composition of the present invention is described in Table 1 below. TABLE 1 Ingredient Amount Weight Percent Tetracaine 1.8 g 6 Propylene Glycol 3.0 ml 10 Sodium Carboxymethyl cellulose- 1.2 g 4 USP Medium Viscosity POLYOX WSR 301 1.5 g 5 Plastibase 22.5 g qs

Sodium carboxymethyl cellulose in an amount of 1.2 g, 1.5 g of POLYOX WSR 301 and 2.0 g of tetracaine were ground in separate glass mortars to a fine powder and set aside. Ten percent extra tetracaine was weighed out because some of the tetracaine adhered to the mortar. By starting with 10% extra, the ground tetracaine available for transfer resulted in a 6 wt % composition.

Plastibase in an amount of 11.25 g was placed in a 200 ml beaker and the beaker placed directly onto a hotplate. The temperature of the hot plate was set on its lowest position. The Plastibase was gently heated until it became soft and semi-fluid. At which point, the Plastibase was workable for compounding purposes. Plastibase melts at about 82° F. Heating was stopped before the Plastibase totally melted as separation occurs and Plastibase will not resume its original consistency when cooled.

The ground sodium carboxymethylcellulose was added in small portions to the heated Plastibase with stirring after each addition to ensure a uniform mix. The beaker was removed from the heat and the mixture cooled.

On an ointment slab, 1.8 g of the finely ground tetracaine was worked with 0.75 ml of propylene glycol (25% of the total propylene glycol specified in Table 1). The tetracaine and propylene glycol mixture was combined with 11.25 g of Plastibase via geometric dilution. The cooled Plastibase and sodium carboxymethylcellulose mixture was then worked into the tetracaine, propylene glycol and Plastibase mixture via geometric dilution.

In a glass mortar the ground POLYOX WSR 301 was wetted with 2.25 ml of propylene glycol (75% of the total propylene glycol specified in Table 1).

The POLYOX WSR 301 and propylene glycol mixture was then incorporated via geometric dilution with the other ingredients previously mixed together on the ointment slab to form 30 g of topical anesthetic paste.

The topical anesthetic paste prepared as described above was then placed in ointment jars and refrigerated. Under refrigeration, the topical anesthetic paste was still effective after six months.

EXAMPLE 2

Several healthy volunteers were recruited from members of a professional dental staff. Approximately 10 mg of paste as prepared in Example 1 was applied to the muco-buccal fold in the maxillary molar region of each subject with a cotton applicator following drying of the mucosa.

All of the subjects reported profound anesthesia at the application site which persisted for approximately 1 to 1-½ hours depending on the subject's metabolism and level of physical activity.

EXAMPLE 3

Prior to infiltration with an injectable anesthetic, approximately 10 mg of topical anesthetic from Example 1 was applied with a Q-tip to the site of injection. The topical anesthetic was rubbed over the mucosa for approximately 10 seconds. The Q-tip was then removed and three to five minutes allowed to lapse before Novocain was injected with a needle.

The subjects reported that they felt no pain upon injection and no taste was perceived. Saliva production was not stimulated and the field remained dry.

Some practitioners have observed that less injectable anesthetic was required to achieve complete anesthesia.

EXAMPLE 4

Approximately 10 mg of paste as prepared in Example 1 was applied to the buccal and to the lingual or to the buccal and to the palatal sides of a tooth prior to removing a crown or bridge. When the tooth had previously received root canal therapy, no injection was required and the patients reported no discomfort in preparing the tooth for a new crown or bridge. When benzocaine 20 wt % was used as the topical anesthetic, most patients required an injection.

EXAMPLE 5

When approximately 10 mg of paste as prepared in Example 1 was applied to the buccal side and 16 mg of paste was applied to the palate, dental scaling and root planing of the maxilla dentition in pockets up to 6-7 mm was accomplished without a palatal injection being needed. In the past, a palatal injection was usually made before attempting scaling and root planing. Painful palatal injection was thus avoided by applying the subject topical anesthetic.

Patients with pockets deeper than about 7 mm are generally referred to a periodontist.

EXAMPLE 6

Fear of syringes and needle insertions is very common among children and a bad dental experience may have a negative impact on the child's willingness to attend to dental care in the future. In pediatric patients, tissue retained extractions of the primary dentition have been accomplished without injection by application of 10 mg of paste as prepared in Example 1 to the tissue supporting the tooth.

EXAMPLE 7

A topical anesthetic was prepared with benzocaine 20 wt % in the vehicle described in Example 1. When the anesthetic was applied as described in Example 2, the subjects reported that the anesthetic effect was not as pronounced as with commercially available benzocaine 20 wt % in gel form. A topical anesthetic was also prepared with 3 wt % lidocaine in the vehicle described in Example 1. When applied as described in Example 2, the subjects reported that the anesthetic effect was better than with 20 wt % benzocaine in the vehicle but that the taste was bitter. In addition, the anesthetic effect only lasted about 10 to 15 minutes which is not enough for many dental procedures.

In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained. As various changes could be made in the above compositions without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense. 

1. A topical anesthetic for use in producing local anesthesia when applied to the oral mucosa prior to a dental treatment, said topical anesthetic comprising tetracaine in particulate form suspended in a plasticized hydrocarbon gel and in admixture with a mucoadhesive.
 2. The topical anesthetic of claim 1 wherein the tetracaine is present in an amount from about 3.0 to about 10.0 percent by weight.
 3. The topical anesthetic of claim 2 wherein the plasticized hydrocarbon gel comprises polyethylene and mineral oil.
 4. The topical anesthetic of claim 3 wherein the mucoadhesive comprises a high molecular weight poly(ethylene oxide) homopolymer in combination with a second water soluble mucoadhesive.
 5. The topical anesthetic of claim 4 wherein the second water soluble mucoadhesive is sodium carboxymethylcellulose.
 6. The topical anesthetic of claim 1 further comprising a penetration enhancer.
 7. The topical anesthetic of claim 6 wherein the penetration enhance is propylene glycol.
 8. A topical anesthetic for use in producing local anesthesia in about three to five minutes when applied to the oral mucosa prior to a dental treatment, said topical anesthetic comprising tetracaine in an amount from about 4 wt % to about 8 wt %, a high molecular weight poly(ethylene oxide) homopolymer in an amount from about 3 wt % to about 8 wt % and a penetration enhancer comprising an alcohol in an amount from about 5 wt % to 15 wt % in a plasticized hydrocarbon gel.
 9. The topical anesthetic of claim 8 wherein the poly(ethylene oxide) homopolymer has a molecular weight about 4,000,000.
 10. The topical anesthetic of claim 8 further comprising a second water soluble mucoadhesive in addition to the poly(ethylene oxide), said second water soluble mucoadhesive being a cellulose polymer.
 11. The topical anesthetic of claim 10 wherein the poly(ethylene oxide) is present in an amount of about 5 wt % and the cellulose polymer is sodium carboxymethylcellulose and is present in an amount of about 4 wt %.
 12. The topical anesthetic of claim 11 wherein the alcohol penetration enhancer is a glycol.
 13. The topical anesthetic of claim 12 wherein the glycol is propylene glycol and is present in an amount of about 10 wt %.
 14. The topical anesthetic of claim 13 having a consistency of a paste and an anesthetic duration of about one to one and one-hours. 